A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer

作者: E. Kieback , J. Charo , D. Sommermeyer , T. Blankenstein , W. Uckert

DOI: 10.1073/PNAS.0710198105

关键词:

摘要: By transfer of T cell receptor (TCR) genes, antigen specificity cells can be redirected to target any antigen. Adoptive TCR-redirected into patients has shown promising results. However, this immunotherapy bears the risk autoreactive side effects if TCR recognizes antigens on self-tissue. Here, we introduce a safeguard based TCR-intrinsic depletion mechanism eliminate in vivo. introduction 10-aa tag human c-myc protein murine (OT-I, P14) and (gp100) sequences, were able deplete that transduced with these myc-tagged TCRs tag-specific antibody vitro. modified maintained equal properties compared wild-type concerning binding effector function. More importantly, therapeutic vivo adoptively transferred rescued mice showing severe signs autoimmune insulitis from lethal diabetes. This allows termination adoptive therapy case effects.

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